Not ready for prime time: the three critical challenges for IPS cells

TUMORIGENICITY

Those of us who work with IPS cells are very excited about their potential for use in regenerative medicine therapies. One serious hurdle we have talked about in the past is tumorigenicity.

COST

Another hurdle that is far less discussed, but is equally critical, is the potential cost of IPS cell based therapies.

The therapeutic advantage of IPS cells over ESC would be that the IPS cells would be patient specific and would require no immunosuppression. However, that’s a double-edged sword because it means that every patient would receive his or her own custom therapy. No ‘off the shelf’ products here as is sometimes referred to batch-prepared hESC-based allo-therapies that can be given to any patient.

What this means is that for any given patient, in essence a new IPS cell therapy must be created each time. The same hypothetical FDA-approved protocol can be used to make the IPS cells for different patients, but you must start from scratch every time with the patient’s own somatic cells. You must grow the somatic cells, bank them, make IPS cells from them, and then test the efficacy and safety of the IPS cell-derived differentiated cells every time before using them. The putative IPS cells have to be validated as IPS cells in numerous, expensive ways including teratoma formation for every patient’s IPS cells. Just because IPS cells derived one month from Patient A are safe, it does not mean that IPS cell derivatives made using the same protocol next month from Patient B can be assumed to be safe.

The cost of an IPS cell-based therapeutic drug could easily exceed $100,000 per patient as it is likely to be more expensive than Provenge, the prostate cancer therapy from Dendreon that costs $93K. For scientists and patient advocates such as myself (I am both), cost comes secondary to efficacy and safety. Also, if you can substantially ameliorate or even cure a patient of a serious illness, from an economics perspective the $100K price tag for IPS cell drugs could actually be reasonable and save money in the long run. But the cost of therapies is critically important to make them available to the widest number of those in need. Will insurance companies and medicare cover such high costs of IPS cell therapies? If not, how many people can actually afford that personally? With hospital costs, I’d guess IPS cell therapies could cost a quarter of a million a patient.

While the hospital costs for a hESC-based treatment would be no different, the actual hESC-based cell drug itself would be far more affordable since it could be batch produced, validated, and safety tested, as was the case with GRNOPC1 from Geron. This represents a critically important advantage for hESC-based therapies over hypothetical IPS cell therapies.

TIMING

The third critical challenge for IPS cell-based therapies is timing. Since new patient-specific therapies must be created and validated for every patient, IPS cell therapies would work only for patients with chronic conditions that provide a stable therapeutic window over months or years.

What this means is that any acute injury or disease as well as any condition with a limited therapeutic window, could likely never be treated using patient-specific IPS cells. Such conditions would have to be treated using allotransplants of batch prepared cells. This is a key advantage of the hESC approach.

A good example is the case of spinal cord injury, during which there is only, at least currently, a few week window of time for treatment. IPS cells could not be produced and validated from any given patient in less than 3-6 months, and that is likely an underestimation. Other conditions that must be treated very quickly include traumatic brain injury, stroke, heart attack, some types of cancer, and serious acute bone injury to name just a few. Together, these represent millions of patients that can not be helped by patient-specific IPS cell treatments.

IPS cells represent an exciting, relatively new approach to regenerative medicine. I am optimistic that for some conditions IPS cell-based therapies will provide treatments and cures in the future, but it could be a while and they are not a panacea. So, we clearly also need hESC-based therapies as well.